The hormone erythropoietin plays a major role in regulating erythropoiesis, the formation of red blood cells, and deficiencies of erythropoietin result in anemia. Detailed studies of the hormone and attempts at replacement therapy have been difficult due to the scarcity of purified material.
Normal production of human red blood cells requires the secretion of erythropoietin by the kidney, apparently as the mature glycoprotein. In the steady state this hormone circulates in the blood at a concentration of 10 to 18 milliunits (128-230 picograms) per milliliter, and with the stimulus of severe tissue hypoxia (oxygen deficiency) the levels may increase as much as 1000-fold. The elevated hormone level triggers proliferation and differentiation of a population of receptive stem cells in the bone marrow, stimulates hemoglobin synthesis in maturing erythroid cells, and accelerates release of red cells from the marrow into circulation, thereby increasing the red cell mass and ameliorating the hypoxic conditions. Patients with deficiencies of erythropoietin, such as those with chronic renal failure, often suffer severe anemia.
Erythropoietin is a glycoprotein of 34-38 kd with approximately 40% of its molecular weight provided by carbohydrate. At least one disulfide bridge is required for activity. Little is known about the structure of this hormone, and the details of its synthesis are not well understood. Recent isolations of cDNA and genomic clones provide opportunities to analyze control of erythropoietin production, but the expression of biologically active human erythropoietin in sufficient quantities for replacement therapy has not been achieved.